The Syrian Observatory for Human Rights said IS had "forced out" some 30,000 residents after seizing Shuheil on Thursday from Al-Qaeda affiliate Al-Nusra Front.
Another 30,000 residents have been forced from their homes in the towns of Khosham and Tabia Jazeera, also in eastern Deir Ezzor province, the Britain-based NGO said.
"Some 30,000 residents of the town of Shuheil, the former stronghold of Al-Nusra Front, have been forced out by the Islamic State," the group said.
IS has seized large swathes of territory in Syria and neighbouring Iraq, declaring the land it holds to be an Islamic "caliphate", and its leader the ruler of all Muslims.
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The Observatory said IS had prevented some 30,000 people from returning to their homes in two other towns in Deir Ezzor, Khosham and Tabia Jazeera, which it captured in late June.
On a Facebook page, activists from Shuheil said IS had ordered all residents to leave, and entered in armoured cars and tanks "because of their fear and cowardice".
Activists said residents feared IS fighters planned to loot their homes, and the Observatory said the large displacement had left thousands sleeping in the open, with food and water shortages.
Elsewhere in the region, the group said negotiations were under way over the fate of some 83,000 people living in three towns in Deir Ezzor after IS advances in the surrounding area.